ACE inhibitor drug reduces heart failure in high-risk patients

The drug ramipril significantly reduced the onset of debilitating and often-fatal heart failure in a large group of high-risk patients, researchers report in today’s rapid access issue of Circulation: Journal of the American Heart Association.

Ramipril, trade-named Altace, is one of a family of high blood pressure medications known as ACE inhibitors. The drugs reduce the risk of death from heart failure – the inability of a weakened or damaged heart to pump enough blood through the body – in people who suffer heart attacks. The American Heart Association estimates that nearly 5 million people in the United States have congestive heart failure.

“This trial extends the benefits of ACE inhibitors beyond what has been previously proven,” says lead author Malcolm Arnold, M.D., “It shows, for the first time, that heart failure can be prevented in a broad range of high risk patients.”

Researchers found that ramipril reduced the risk of heart failure by 23 percent in patients with cardiovascular disease who still had normal heart pumping function and no previous heart failure. Patients who received the drug also had a lower rate of hospitalization and death because of heart failure.

“The reduction of heart failure in people treated with ramipril was consistent in all major subgroups,” says Arnold, professor of medicine, physiology, and pharmacology at the University of Western Ontario and a cardiologist at the London Health Sciences Center in London, Ontario, Canada. “These included patients over 65 years, females, and patients without known hypertension or diabetes.” The trial is from the Heart Outcomes Prevention Evaluation (HOPE) study, a randomized trial that followed 9,541 high-risk cardiovascular patients age 55 and older at 267 centers in 19 countries in the Americas and Europe.

In the new analysis, the researchers used data from 9,297 of the HOPE participants who had randomly received either 10 milligrams of ramipril or a placebo daily and were followed for an average of 4.5 years. Their average age was 66 and 73 percent were males. Fifty-three percent had a previous heart attack, 47 percent had a history of hypertension, and 38 percent had diabetes – all risk factors for heart failure.

Researchers defined heart failure as any of the following: poor heart pumping that caused death, or required hospitalization or treatment with ACE inhibitors as determined by a physician, or the appearance of the disease’s typical signs and symptoms. One or more of these components occurred in 951 (10.2 percent) of the participants during the follow-up period.

Ramipril reduced the rate of heart failure by a significant 22 percent in the 8,315 patients who did not suffer a heart attack. Among the 1,029 people who had a heart attack, those taking ramipril had a 13 percent lower rate of heart failure, although this finding did not reach statistical significance, Arnold says.

In addition, patients treated with ramipril whose systolic blood pressure (the upper number in a blood pressure reading) was above the median had a 33 percent reduction in risk of heart failure compared to a 9 percent reduction for those below the median.

In an accompanying editorial, Jennifer V. Linseman, Ph.D., and Michael R. Bristow, M.D., Ph.D., of the University of Colorado Health Sciences Center in Denver, note that for a majority of the participants in this analysis were classified with heart failure if their symptoms were severe enough that they need to be treated with ACE inhibitors.

This is a “softer endpoint that death or hospitalization . . . .” they write. “Therefore results, while still encouraging, should be viewed with some caution.”

Taken with previous results from the HOPE study, they say: “these data support the idea that ACE inhibitors exert a measurable cardiovascular-protective effect in a broad range of patients at high-risk of cardiovascular complications, and these effects are additional to and independent of blood pressure lowering.”

Arnold’s co-authors are Salim Yusuf, M.D.; James Young, M.D.; James Mathew, M.D.; David Johnstone, M.D.; Alvaro Avezum, M.D.; Eva Lonn, M.D.; Janice Pogue; and Jackie Bosch on behalf of the HOPE investigators.

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